Lan Yong, Dong Min, Li Yongjun, Diao Yongpeng, Chen Zuoguang, Li Yangfang
Department of Vascular Surgery, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital, Beijing 100730, P.R. China.
Department of Cardiology, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital, Beijing 100730, P.R. China.
Mol Ther Nucleic Acids. 2021 Jan 26;23:1323-1333. doi: 10.1016/j.omtn.2021.01.023. eCollection 2021 Mar 5.
Maintaining the health of the endothelium is of critical importance to prevention against cell aging. The current study was performed to clarify the role of sirtuin1 (SIRT1) in platelet phagocytosis in cell aging and identified its downstream molecular mechanism. Platelet phagocytosis by human endometrial microvascular endothelial cells (HEMECs) was characterized by transmission electron and fluorescence microscopy. Functional experiments were conducted to examine platelet phagocytosis and cell aging using the overexpression or knockdown plasmids of SIRT1 and G alpha-interacting, vesicle-associated protein (GIRDIN) as well as Akt inhibitor and activator. It was found that SIRT1 facilitated platelet phagocytosis by HEMECs, contributing to inhibition of cell aging. Akt activation facilitated platelet phagocytosis and repressed cell aging. GIRDIN overexpression accelerated platelet phagocytosis by HEMECs, leading to a delay in cell aging. GIRDIN phosphorylation at Ser1417 was induced by Akt activation, while activation of Akt was induced by SIRT1-mediated deacetylation, consequently augmenting platelet phagocytosis and delaying cell aging. Taken together, SIRT1 delayed aging of HEMECs by deacetylating Akt, phosphorylating GIRDIN, and inducing platelet phagocytosis. The study highlights a possible target for the prevention of HEMEC aging.
维持内皮细胞的健康对于预防细胞衰老至关重要。本研究旨在阐明沉默调节蛋白1（SIRT1）在细胞衰老过程中血小板吞噬作用中的作用，并确定其下游分子机制。通过透射电子显微镜和荧光显微镜对人子宫内膜微血管内皮细胞（HEMECs）的血小板吞噬作用进行了表征。使用SIRT1和Gα相互作用、囊泡相关蛋白（GIRDIN）的过表达或敲低质粒以及Akt抑制剂和激活剂进行功能实验，以检测血小板吞噬作用和细胞衰老。结果发现，SIRT1促进了HEMECs的血小板吞噬作用，有助于抑制细胞衰老。Akt激活促进了血小板吞噬作用并抑制了细胞衰老。GIRDIN过表达加速了HEMECs的血小板吞噬作用，导致细胞衰老延迟。Akt激活诱导了Ser1417位点的GIRDIN磷酸化，而SIRT1介导的去乙酰化诱导了Akt的激活，从而增强了血小板吞噬作用并延迟了细胞衰老。综上所述，SIRT1通过使Akt去乙酰化、使GIRDIN磷酸化并诱导血小板吞噬作用，延缓了HEMECs的衰老。该研究突出了一个预防HEMECs衰老的可能靶点。
